847 resultados para Jeff Godfrey
Resumo:
Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-b (TGFb)1, TGFb2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P < 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P < 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1–28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear.
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The turbulent mixing in thin ocean surface boundary layers (OSBL), which occupy the upper 100 m or so of the ocean, control the exchange of heat and trace gases between the atmosphere and ocean. Here we show that current parameterizations of this turbulent mixing lead to systematic and substantial errors in the depth of the OSBL in global climate models, which then leads to biases in sea surface temperature. One reason, we argue, is that current parameterizations are missing key surface-wave processes that force Langmuir turbulence that deepens the OSBL more rapidly than steady wind forcing. Scaling arguments are presented to identify two dimensionless parameters that measure the importance of wave forcing against wind forcing, and against buoyancy forcing. A global perspective on the occurrence of waveforced turbulence is developed using re-analysis data to compute these parameters globally. The diagnostic study developed here suggests that turbulent energy available for mixing the OSBL is under-estimated without forcing by surface waves. Wave-forcing and hence Langmuir turbulence could be important over wide areas of the ocean and in all seasons in the Southern Ocean. We conclude that surfacewave- forced Langmuir turbulence is an important process in the OSBL that requires parameterization.
Resumo:
Three prominent quasi-global patterns of variability and change are observed using the Met Office's sea surface temperature (SST) analysis and almost independent night marine air temperature analysis. The first is a global warming signal that is very highly correlated with global mean SST. The second is a decadal to multidecadal fluctuation with some geographical similarity to the El Niño–Southern Oscillation (ENSO). It is associated with the Pacific Decadal Oscillation (PDO), and its Pacific-wide manifestation has been termed the Interdecadal Pacific Oscillation (IPO). We present model investigations of the relationship between the IPO and ENSO. The third mode is an interhemispheric variation on multidecadal timescales which, in view of climate model experiments, is likely to be at least partly due to natural variations in the thermohaline circulation. Observed climatic impacts of this mode also appear in model simulations. Smaller-scale, regional atmospheric phenomena also affect climate on decadal to interdecadal timescales. We concentrate on one such mode, the winter North Atlantic Oscillation (NAO). This shows strong decadal to interdecadal variability and a correspondingly strong influence on surface climate variability which is largely additional to the effects of recent regional anthropogenic climate change. The winter NAO is likely influenced by both SST forcing and stratospheric variability. A full understanding of decadal changes in the NAO and European winter climate may require a detailed representation of the stratosphere that is hitherto missing in the major climate models used to study climate change.
Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system
Resumo:
BACKGROUND: Bile acids (BAs) regulate cells by activating nuclear and membrane-bound receptors. G protein coupled bile acid receptor 1 (GpBAR1) is a membrane-bound G-protein-coupled receptor that can mediate the rapid, transcription-independent actions of BAs. Although BAs have well-known actions on motility and secretion, nothing is known about the localization and function of GpBAR1 in the gastrointestinal tract. METHODS: We generated an antibody to the C-terminus of human GpBAR1, and characterized the antibody by immunofluorescence and Western blotting of HEK293-GpBAR1-GFP cells. We localized GpBAR1 immunoreactivity (IR) and mRNA in the mouse intestine, and determined the mechanism by which BAs activate GpBAR1 to regulate intestinal motility. KEY RESULTS: The GpBAR1 antibody specifically detected GpBAR1-GFP at the plasma membrane of HEK293 cells, and interacted with proteins corresponding in mass to the GpBAR1-GFP fusion protein. GpBAR1-IR and mRNA were detected in enteric ganglia of the mouse stomach and small and large intestine, and in the muscularis externa and mucosa of the small intestine. Within the myenteric plexus of the intestine, GpBAR1-IR was localized to approximately 50% of all neurons and to >80% of inhibitory motor neurons and descending interneurons expressing nitric oxide synthase. Deoxycholic acid, a GpBAR1 agonist, caused a rapid and sustained inhibition of spontaneous phasic activity of isolated segments of ileum and colon by a neurogenic, cholinergic and nitrergic mechanism, and delayed gastrointestinal transit. CONCLUSIONS & INFERENCES: G protein coupled bile acid receptor 1 is unexpectedly expressed in enteric neurons. Bile acids activate GpBAR1 on inhibitory motor neurons to release nitric oxide and suppress motility, revealing a novel mechanism for the actions of BAs on intestinal motility.
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Satellite-based Synthetic Aperture Radar (SAR) has proved useful for obtaining information on flood extent, which, when intersected with a Digital Elevation Model (DEM) of the floodplain, provides water level observations that can be assimilated into a hydrodynamic model to decrease forecast uncertainty. With an increasing number of operational satellites with SAR capability, information on the relationship between satellite first visit and revisit times and forecast performance is required to optimise the operational scheduling of satellite imagery. By using an Ensemble Transform Kalman Filter (ETKF) and a synthetic analysis with the 2D hydrodynamic model LISFLOOD-FP based on a real flooding case affecting an urban area (summer 2007,Tewkesbury, Southwest UK), we evaluate the sensitivity of the forecast performance to visit parameters. We emulate a generic hydrologic-hydrodynamic modelling cascade by imposing a bias and spatiotemporal correlations to the inflow error ensemble into the hydrodynamic domain. First, in agreement with previous research, estimation and correction for this bias leads to a clear improvement in keeping the forecast on track. Second, imagery obtained early in the flood is shown to have a large influence on forecast statistics. Revisit interval is most influential for early observations. The results are promising for the future of remote sensing-based water level observations for real-time flood forecasting in complex scenarios.
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Wide ranging climate changes are expected in the Arctic by the end of the 21st century, but projections of the size of these changes vary widely across current global climate models. This variation represents a large source of uncertainty in our understanding of the evolution of Arctic climate. Here we systematically quantify and assess the model uncertainty in Arctic climate changes in two CO2 doubling experiments: a multimodel ensemble (CMIP3) and an ensemble constructed using a single model (HadCM3) with multiple parameter perturbations (THC-QUMP). These two ensembles allow us to assess the contribution that both structural and parameter variations across models make to the total uncertainty and to begin to attribute sources of uncertainty in projected changes. We find that parameter uncertainty is an major source of uncertainty in certain aspects of Arctic climate. But also that uncertainties in the mean climate state in the 20th century, most notably in the northward Atlantic ocean heat transport and Arctic sea ice volume, are a significant source of uncertainty for projections of future Arctic change. We suggest that better observational constraints on these quantities will lead to significant improvements in the precision of projections of future Arctic climate change.
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Abstract Objective: To systematically review the available evidence on whether national or international agricultural policies that directly affect the price of food influence the prevalence rates of undernutrition or nutrition-related chronic disease in children and adults. Design: Systematic review. Setting: Global. Search strategy: We systematically searched five databases for published literature (MEDLINE, EconLit, Agricola, AgEcon Search, Scopus) and systematically browsed other databases and relevant organisational websites for unpublished literature. Reference lists of included publications were hand-searched for additional relevant studies. We included studies that evaluated or simulated the effects of national or international food-price-related agricultural policies on nutrition outcomes reporting data collected after 1990 and published in English. Primary and secondary outcomes: Prevalence rates of undernutrition (measured with anthropometry or clinical deficiencies) and overnutrition (obesity and nutrition-related chronic diseases including cancer, heart disease and diabetes). Results: We identified a total of four relevant reports; two ex post evaluations and two ex ante simulations. A study from India reported on the undernutrition rates in children, and the other three studies from Egypt, the Netherlands and the USA reported on the nutrition related chronic disease outcomes in adults. Two of the studies assessed the impact of policies that subsidised the price of agricultural outputs and two focused on public food distribution policies. The limited evidence base provided some support for the notion that agricultural policies that change the prices of foods at a national level can have an effect on population-level nutrition and health outcomes. Conclusions: A systematic review of the available literature suggests that there is a paucity of robust direct evidence on the impact of agricultural price policies on nutrition and health.
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TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid, DCA, taurolithocholic acid, TLCA) and the selective agonists oleanolic acid (OA) and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide (CCDC) stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, assessed by confocal microscopy. DCA, TLCA and OA did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, determined by bioluminescence resonance energy transfer. CCDC stimulated a low level of TGR5 interaction with β-arrestin2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of extracellular signal regulated kinase (ERK1/2). BRET analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.
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Television’s long-form storytelling has the potential to allow the rippling of music across episodes and seasons in interesting ways. In the integration of narrative, music and meaning found in The O.C. (Fox, FOX 2003-7), popular song’s allusive and referential qualities are drawn upon to particularly televisual ends. At times embracing its ‘disruptive’ presence, at others suturing popular music into narrative, at times doing both at once. With television studies largely lacking theories of music, this chapter draws on film music theory and close textual analysis to analyse some of the programme's music moments in detail. In particular it considers the series-spanning use of Jeff Buckley’s cover of ‘Hallelujah’ (and its subsequent oppressive presence across multiple televisual texts), the end of episode musical montage and the use of recurring song fragments as theme within single episodes. In doing so it highlights music's role in the fragmentation and flow of the television aesthetic and popular song’s structural presence in television narrative. Illustrating the multiplicity of popular song’s use in television, these moments demonstrate song’s ability to provide narrative commentary, yet also make particular use of what Ian Garwood describes as the ability of ‘a non-diegetic song to exceed the emotional range displayed by diegetic characters’ (2003:115), to ‘speak’ for characters or to their feelings, contributing to both teen TV’s melodramatic affect and narrative expression.
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The rise of food security up international political, societal and academic agendas has led to increasing interest in novel means of improving primary food production and reducing waste. There are however, also many ‘post-farm gate’ activities that are critical to food security, including processing, packaging, distributing, retailing, cooking and consuming. These activities all affect a range of important food security elements, notably availability, affordability and other aspects of access, nutrition and safety. Addressing the challenge of universal food security, in the context of a number of other policy goals (e.g. social, economic and environmental sustainability), is of keen interest to a range of UK stakeholders but requires an up-to-date evidence base and continuous innovation. An exercise was therefore conducted, under the auspices of the UK Global Food Security Programme, to identify priority research questions with a focus on the UK food system (though the outcomes may be broadly applicable to other developed nations). Emphasis was placed on incorporating a wide range of perspectives (‘world views’) from different stakeholder groups: policy, private sector, non-governmental organisations, advocacy groups and academia. A total of 456 individuals submitted 820 questions from which 100 were selected by a process of online voting and a three-stage workshop voting exercise. These 100 final questions were sorted into 10 themes and the ‘top’ question for each theme identified by a further voting exercise. This step also allowed four different stakeholder groups to select the top 7–8 questions from their perspectives. Results of these voting exercises are presented. It is clear from the wide range of questions prioritised in this exercise that the different stakeholder groups identified specific research needs on a range of post-farm gate activities and food security outcomes. Evidence needs related to food affordability, nutrition and food safety (all key elements of food security) featured highly in the exercise. While there were some questions relating to climate impacts on production, other important topics for food security (e.g. trade, transport, preference and cultural needs) were not viewed as strongly by the participants.
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There is a growing need for massive computational resources for the analysis of new astronomical datasets. To tackle this problem, we present here our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, AstroGrid) and the computa- tional grid (e.g. TeraGrid, COSMOS etc.). We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of compu- tational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We discuss our planned usages of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS data and mas- sive model-fitting of millions of CMBfast models to WMAP data. We also discuss other applications including the determination of the XMM Cluster Survey selection function and the construction of new WMAP maps.
Resumo:
We outline our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, Astro- Grid) and the computational grid. We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of computational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We present our planned usage of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS, as well as fitting over a million CMBfast models to the WMAP data.
Resumo:
The infant gut microbiota plays an important role in the development of the infant immune and gastrointestinal systems. We investigated whether increased salmon consumption during pregnancy, maternal weight gain during pregnancy or infant mode of feeding alter markers of gut immune defence and inflammation. Women (n = 123) who rarely ate oily fish were randomly assigned to remain on their habitual diet or to consume two 150 g portions of farmed salmon per week from 20 weeks pregnancy until delivery. At 38 weeks gestation the women (n = 75) provided a faecal sample and on days 7, 14, 28 and 84 post-partum, faecal samples were collected from the infants (n = 38). Fluorescence in situ hybridisation was used to determine the composition of the faecal microbiota and ELISA to measure faecal sIgA and calprotectin concentrations. There was no effect of salmon consumption on the faecal microbiota of the mothers or on faecal sIgA and calprotectin concentrations in either mothers or infants. Degree of weight gain influenced the maternal faecal microbiota and mode of infant feeding influenced the infant faecal microbiota. Faecal samples from infants in the salmon group tended to have lower counts of Atopobium cluster compared with those in the control group (P = 0.097). This difference was significant in formula-fed infants (P < 0.05), but not exclusively breast-fed infants. In conclusion, the impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences were associated with maternal weight gain during pregnancy and infant mode of feeding.
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Anxious mothers’ parenting, particularly transfer of threat information, has been considered important in their children’s risk for social anxiety disorder (SAnxD), and maternal narratives concerning potential social threat could elucidate this contribution. Maternal narratives to their pre-school 4-5 year-old children, via a picture book about starting school, were assessed in socially anxious (N=73), and non-anxious (N=63) mothers. Child representations of school were assessed via Doll Play (DP). After one school term, mothers (CBCL) and teachers (TRF) reported on child internalizing problems, and child SAnxD was assessed via maternal interview. Relations between these variables, infant behavioral inhibition, and attachment, were examined. Socially anxious mothers showed more negative (higher threat attribution), and less supportive (lower encouragement) narratives, than controls, and their children’s DP representations, SAnxD and CBCL scores were more adverse. High narrative threat predicted child SAnxD; lower encouragement predicted negative child CBCL scores and, particularly for behaviorally inhibited children, TRF scores and DP representations. In securely attached children, CBCL scores and risk for SAnxD were affected by maternal anxiety and threat attributions, respectively. Low encouragement mediated the effects of maternal anxiety on child DP representations, and CBCL scores. Maternal narratives are affected by social anxiety, and contribute to adverse child outcome.